The Molecular Structure and Self-Assembly Behavior of Reductive Amination of Oxidized Alginate Derivative for Hydrophobic Drug Delivery

• Published in: Molecules (Basel, Switzerland) Switzerland), 2021-09, Vol.26 (19), p.5821
• Main Authors: Chen, Xiuqiong, Zhu, Qingmei, Li, Zhengyue, Yan, Huiqiong, Lin, Qiang
• Format: Article
• Language: English
• Subjects: Acids; Aggregates; Alginates - chemistry; Alginic acid; Amination; Amines - chemistry; Animals; Biocompatibility; Controlled release; Cytotoxicity; Diffusion rate; Drug Carriers - chemistry; Drug delivery; Drug Delivery Systems; Fluorescence; Gravimetric analysis; Hydrogels; Hydrogen bonds; hydrophobic drug delivery; Hydrophobicity; Ibuprofen; Ibuprofen - administration & dosage; Ibuprofen - chemistry; Infrared spectrometers; Light scattering; Macrophages; Macrophages - drug effects; Mice; Micelles; Molecular Structure; NMR; Nonsteroidal anti-inflammatory drugs; Nuclear magnetic resonance; Oxidation; Pharmaceuticals; Photon correlation spectroscopy; RAW 264.7 Cells; reductive amination of oxidized alginate derivative; Rheological properties; Rheology; Rigid structures; Self-assembly; self-assembly behavior; Shearing; Sodium alginate; Sodium chloride; Spectrum analysis; Surfactants; systematic characterization; Thermal analysis; X-ray diffraction; Zeta potential
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26195821

On account of the rigid structure of alginate chains, the oxidation-reductive amination reaction was performed to synthesize the reductive amination of oxidized alginate derivative (RAOA) that was systematically characterized for the development of pharmaceutical formulations. The molecular structure and self-assembly behavior of the resultant RAOA was evaluated by an FT-IR spectrometer, a H NMR spectrometer, X-ray diffraction (XRD), thermal gravimetric analysis (TGA), a fluorescence spectrophotometer, rheology, a transmission electron microscope (TEM) and dynamic light scattering (DLS). In addition, the loading and in vitro release of ibuprofen for the RAOA microcapsules prepared by the high-speed shearing method, and the cytotoxicity of the RAOA microcapsules against the murine macrophage RAW264.7 cell were also studied. The experimental results indicated that the hydrophobic octylamine was successfully grafted onto the alginate backbone through the oxidation-reductive amination reaction, which destroyed the intramolecular hydrogen bond of the raw sodium alginate (SA), thereby enhancing its molecular flexibility to achieve the self-assembly performance of RAOA. Consequently, the synthesized RAOA displayed good amphiphilic properties with a critical aggregation concentration (CAC) of 0.43 g/L in NaCl solution, which was significantly lower than that of SA, and formed regular self-assembled micelles with an average hydrodynamic diameter of 277 nm (PDI = 0.19) and a zeta potential of about -69.8 mV. Meanwhile, the drug-loaded RAOA microcapsules had a relatively high encapsulation efficiency (EE) of 87.6 % and good sustained-release properties in comparison to the drug-loaded SA aggregates, indicating the good affinity of RAOA to hydrophobic ibuprofen. The swelling and degradation of RAOA microcapsules and the diffusion of the loaded drug jointly controlled the release rate of ibuprofen. Moreover, it also displayed low cytotoxicity against the RAW264.7 cell, similar to the SA aggregates. In view of the excellent advantages of RAOA, it is expected to become the ideal candidate for hydrophobic drug delivery in the biomedical field.